Skip to main content
Erschienen in: Hernia 4/2015

01.08.2015 | Original Article

The effects of Losartan on abdominal wall fascial healing

Erschienen in: Hernia | Ausgabe 4/2015

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Losartan, a commonly used angiotensin II receptor blocker (ARB) for blood pressure control, also impairs cutaneous wound healing. Our current study will analyze how Losartan affects wound healing in the muscle and fascia from both biomechanical and histological aspects.

Methods

A total of 26 Sprague–Dawley rats were separated into one control group (NS, N = 13) and one experimental group (LG, N = 13) to receive normal saline and 40 mg/kg of Losartan by way of gastric lavage, respectively. 7 days later, all animals were subjected to a 5 cm midline laparotomy. The fascia and skin were then closed with 4-0 prolene and 5-0 vicryl. 15 days postoperatively, the animals were sacrificed and the abdominal wall harvested for wound tensiometric test and histological analysis.

Results

All 26 rats survived to the time of necropsy. Tensiometry detected significantly higher wound tensile strength in the NS group (1.6 ± 0.31 N/mm) than in the LG (1.3 ± 0.28 N/mm) group (p = 0.016). Transection histology with trichrome staining demonstrated higher degree of immature fibroplasia inside the wound in the LG group than in the NS group (p = <0.0001). The LG group also had larger incisional gaps than the NG group.

Conclusion

The antihypertensive drug, Losartan, retards wound healing in the abdominal fascia and reduces wound tensile strength in our rat model. Attention should be paid to the potential effects of various medications on fascial wound healing to guarantee optimal surgical outcomes.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Chudnovskii NA, Desnitskaia EV (1984) Optimization of the preoperative diagnosis of herniated lumbar disks. Zh Vopr Neirokhir Im N N Burdenko 6:51–56PubMed Chudnovskii NA, Desnitskaia EV (1984) Optimization of the preoperative diagnosis of herniated lumbar disks. Zh Vopr Neirokhir Im N N Burdenko 6:51–56PubMed
2.
Zurück zum Zitat Umakanthan R, Dubose R, Byrne JG et al (2010) Preoperative optimization of multi-organ failure following acute myocardial infarction and ischemic mitral regurgitation by placement of a transthoracic intra-aortic balloon pump. Heart Surg Forum 13(5):E342–E344PubMedCrossRef Umakanthan R, Dubose R, Byrne JG et al (2010) Preoperative optimization of multi-organ failure following acute myocardial infarction and ischemic mitral regurgitation by placement of a transthoracic intra-aortic balloon pump. Heart Surg Forum 13(5):E342–E344PubMedCrossRef
3.
Zurück zum Zitat Berlauk JF, Abrams JH, Gilmour IJ et al (1991) Preoperative optimization of cardiovascular hemodynamics improves outcome in peripheral vascular surgery. A prospective, randomized clinical trial. Ann Surg 214(3):289–297 (discussion 298–9)PubMedCentralPubMedCrossRef Berlauk JF, Abrams JH, Gilmour IJ et al (1991) Preoperative optimization of cardiovascular hemodynamics improves outcome in peripheral vascular surgery. A prospective, randomized clinical trial. Ann Surg 214(3):289–297 (discussion 298–9)PubMedCentralPubMedCrossRef
4.
Zurück zum Zitat Buse GL, Bucher E, Seeberger MD et al (2009) Perioperative management of chronic medication: to withhold, continue or intensify? Ther Umsch 66(7):509–517PubMedCrossRef Buse GL, Bucher E, Seeberger MD et al (2009) Perioperative management of chronic medication: to withhold, continue or intensify? Ther Umsch 66(7):509–517PubMedCrossRef
5.
Zurück zum Zitat Kim S, Iwao H (2000) Molecular and cellular mechanisms of angiotensin II-mediated cardiovascular and renal diseases. Pharmacol Rev 52(1):11–34PubMed Kim S, Iwao H (2000) Molecular and cellular mechanisms of angiotensin II-mediated cardiovascular and renal diseases. Pharmacol Rev 52(1):11–34PubMed
6.
Zurück zum Zitat Tang HT, Cheng DS, Jia YT et al (2009) Angiotensin II induces type I collagen gene expression in human dermal fibroblasts through an AP-1/TGF-beta1-dependent pathway. Biochem Biophys Res Commun 385(3):418–423PubMedCrossRef Tang HT, Cheng DS, Jia YT et al (2009) Angiotensin II induces type I collagen gene expression in human dermal fibroblasts through an AP-1/TGF-beta1-dependent pathway. Biochem Biophys Res Commun 385(3):418–423PubMedCrossRef
7.
Zurück zum Zitat Dussaillant GR, Gonzalez H, Cespedes C et al (1996) Regression of left ventricular hypertrophy in experimental renovascular hypertension: diastolic dysfunction depends more on myocardial collagen than it does on myocardial mass. J Hypertens 14(9):1117–1123PubMedCrossRef Dussaillant GR, Gonzalez H, Cespedes C et al (1996) Regression of left ventricular hypertrophy in experimental renovascular hypertension: diastolic dysfunction depends more on myocardial collagen than it does on myocardial mass. J Hypertens 14(9):1117–1123PubMedCrossRef
8.
Zurück zum Zitat Yahata Y, Shirakata Y, Tokumaru S et al (2006) A novel function of angiotensin II in skin wound healing. Induction of fibroblast and keratinocyte migration by angiotensin II via heparin-binding epidermal growth factor (EGF)-like growth factor-mediated EGF receptor transactivation. J Biol Chem 281(19):13209–13216PubMedCrossRef Yahata Y, Shirakata Y, Tokumaru S et al (2006) A novel function of angiotensin II in skin wound healing. Induction of fibroblast and keratinocyte migration by angiotensin II via heparin-binding epidermal growth factor (EGF)-like growth factor-mediated EGF receptor transactivation. J Biol Chem 281(19):13209–13216PubMedCrossRef
9.
Zurück zum Zitat de Gusmao FM, Becker C, Carvalho MH et al (2005) Angiotensin II inhibition during myocardial ischemia-reperfusion in dogs: effects on leukocyte infiltration, nitric oxide synthase isoenzymes activity and left ventricular ejection fraction. Int J Cardiol 100(3):363–370PubMedCrossRef de Gusmao FM, Becker C, Carvalho MH et al (2005) Angiotensin II inhibition during myocardial ischemia-reperfusion in dogs: effects on leukocyte infiltration, nitric oxide synthase isoenzymes activity and left ventricular ejection fraction. Int J Cardiol 100(3):363–370PubMedCrossRef
10.
Zurück zum Zitat Arteel GE (2004) “HOPE” for the liver? Mechanistic insight into the role of the renin-angiotensin system in hepatic fibrosis. Hepatology 40(1):263–265PubMedCrossRef Arteel GE (2004) “HOPE” for the liver? Mechanistic insight into the role of the renin-angiotensin system in hepatic fibrosis. Hepatology 40(1):263–265PubMedCrossRef
11.
Zurück zum Zitat Guo L, Richardson KS, Tucker LM et al (2004) Role of the renin-angiotensin system in hepatic ischemia reperfusion injury in rats. Hepatology 40(3):583–589PubMedCrossRef Guo L, Richardson KS, Tucker LM et al (2004) Role of the renin-angiotensin system in hepatic ischemia reperfusion injury in rats. Hepatology 40(3):583–589PubMedCrossRef
12.
Zurück zum Zitat Chen S, Zhou H, Wang L et al (2002) The effect of losartan intervention on the regulation of pulmonary arterial collagen expression by protein kinase C in chronic hypoxic rat models. Zhonghua Nei Ke Za Zhi 41(7):444–449PubMed Chen S, Zhou H, Wang L et al (2002) The effect of losartan intervention on the regulation of pulmonary arterial collagen expression by protein kinase C in chronic hypoxic rat models. Zhonghua Nei Ke Za Zhi 41(7):444–449PubMed
13.
Zurück zum Zitat Arnold SA, Rivera LB, Carbon JG et al (2012) Losartan slows pancreatic tumor progression and extends survival of SPARC-null mice by abrogating aberrant TGFbeta activation. PLoS ONE 7(2):e31384PubMedCentralPubMedCrossRef Arnold SA, Rivera LB, Carbon JG et al (2012) Losartan slows pancreatic tumor progression and extends survival of SPARC-null mice by abrogating aberrant TGFbeta activation. PLoS ONE 7(2):e31384PubMedCentralPubMedCrossRef
14.
Zurück zum Zitat Viswanathan M, Saavedra JM (1992) Expression of angiotensin II AT2 receptors in the rat skin during experimental wound healing. Peptides 13(4):783–786PubMedCrossRef Viswanathan M, Saavedra JM (1992) Expression of angiotensin II AT2 receptors in the rat skin during experimental wound healing. Peptides 13(4):783–786PubMedCrossRef
15.
Zurück zum Zitat Ozturk CN, Tezel E, Yalcin O (2011) Evaluation of the effects of losartan on a random pattern skin flap model in rats. Ulus Travma Acil Cerrahi Derg 17(2):97–102PubMedCrossRef Ozturk CN, Tezel E, Yalcin O (2011) Evaluation of the effects of losartan on a random pattern skin flap model in rats. Ulus Travma Acil Cerrahi Derg 17(2):97–102PubMedCrossRef
16.
Zurück zum Zitat Biondo-Simoes Mde L, Zazula AD, Gomes AB (2006) Influence of arterial hypertension treated with losartan on skin healing in rats. Acta Cir Bras 21(3):144–150PubMedCrossRef Biondo-Simoes Mde L, Zazula AD, Gomes AB (2006) Influence of arterial hypertension treated with losartan on skin healing in rats. Acta Cir Bras 21(3):144–150PubMedCrossRef
17.
Zurück zum Zitat Harth KC, Blatnik JA, Anderson JM et al (2013) Effect of surgical wound classification on biologic graft performance in complex hernia repair: an experimental study. Surgery 153(4):481–492PubMedCrossRef Harth KC, Blatnik JA, Anderson JM et al (2013) Effect of surgical wound classification on biologic graft performance in complex hernia repair: an experimental study. Surgery 153(4):481–492PubMedCrossRef
19.
Zurück zum Zitat Franz MG, Kuhn MA, Wright TE et al (2000) Use of the wound healing trajectory as an outcome determinant for acute wound healing. Wound Repair Regen 8(6):511–516PubMedCrossRef Franz MG, Kuhn MA, Wright TE et al (2000) Use of the wound healing trajectory as an outcome determinant for acute wound healing. Wound Repair Regen 8(6):511–516PubMedCrossRef
20.
Zurück zum Zitat Culbertson EJ, Xing L, Wen Y et al (2011) Loss of mechanical strain impairs abdominal wall fibroblast proliferation, orientation, and collagen contraction function. Surgery 150(3):410–417PubMedCentralPubMedCrossRef Culbertson EJ, Xing L, Wen Y et al (2011) Loss of mechanical strain impairs abdominal wall fibroblast proliferation, orientation, and collagen contraction function. Surgery 150(3):410–417PubMedCentralPubMedCrossRef
21.
Zurück zum Zitat Dubay DA, Franz MG (2003) Acute wound healing: the biology of acute wound failure. Surg Clin North Am 83(3):463–481PubMedCrossRef Dubay DA, Franz MG (2003) Acute wound healing: the biology of acute wound failure. Surg Clin North Am 83(3):463–481PubMedCrossRef
22.
Zurück zum Zitat Dubay DA, Wang X, Kirk S et al (2004) Fascial fibroblast kinetic activity is increased during abdominal wall repair compared to dermal fibroblasts. Wound Repair Regen 12(5):539–545PubMedCrossRef Dubay DA, Wang X, Kirk S et al (2004) Fascial fibroblast kinetic activity is increased during abdominal wall repair compared to dermal fibroblasts. Wound Repair Regen 12(5):539–545PubMedCrossRef
23.
Zurück zum Zitat Franz MG, Smith PD, Wachtel TL et al (2001) Fascial incisions heal faster than skin: a new model of abdominal wall repair. Surgery 129(2):203–208PubMedCrossRef Franz MG, Smith PD, Wachtel TL et al (2001) Fascial incisions heal faster than skin: a new model of abdominal wall repair. Surgery 129(2):203–208PubMedCrossRef
25.
Zurück zum Zitat Klinge U, Zheng H, Si ZY et al (1999) Synthesis of type I and III collagen, expression of fibronectin and matrix metalloproteinases-1 and -13 in hernial sac of patients with inguinal hernia. Int J Surg Investig 1(3):219–227PubMed Klinge U, Zheng H, Si ZY et al (1999) Synthesis of type I and III collagen, expression of fibronectin and matrix metalloproteinases-1 and -13 in hernial sac of patients with inguinal hernia. Int J Surg Investig 1(3):219–227PubMed
26.
Zurück zum Zitat Novitsky YW, Rosen MJ (2012) The biology of biologics: basic science and clinical concepts. Plast Reconstr Surg 130(5 Suppl 2):9S–17SPubMedCrossRef Novitsky YW, Rosen MJ (2012) The biology of biologics: basic science and clinical concepts. Plast Reconstr Surg 130(5 Suppl 2):9S–17SPubMedCrossRef
27.
Zurück zum Zitat Yaman I, Derici H, Kara C et al (2012) Effects of resveratrol on incisional wound healing in rats. Surg Today 5:1–6 Yaman I, Derici H, Kara C et al (2012) Effects of resveratrol on incisional wound healing in rats. Surg Today 5:1–6
28.
Zurück zum Zitat Aren A, Gökçe A, Gökçe FS (2011) Roles of matrix metalloproteinases in the etiology of inguinal hernia. Hernia 15(6):667–671PubMedCrossRef Aren A, Gökçe A, Gökçe FS (2011) Roles of matrix metalloproteinases in the etiology of inguinal hernia. Hernia 15(6):667–671PubMedCrossRef
29.
Zurück zum Zitat Ren M, Hao S, Yang C et al (2013) Angiotensin II regulates collagen metabolism through modulating tissue inhibitor of metalloproteinase-1 in diabetic skin tissues. Diabetes Vasc Dis Res 10(5):426–435CrossRef Ren M, Hao S, Yang C et al (2013) Angiotensin II regulates collagen metabolism through modulating tissue inhibitor of metalloproteinase-1 in diabetic skin tissues. Diabetes Vasc Dis Res 10(5):426–435CrossRef
Metadaten
Titel
The effects of Losartan on abdominal wall fascial healing
Publikationsdatum
01.08.2015
Erschienen in
Hernia / Ausgabe 4/2015
Print ISSN: 1265-4906
Elektronische ISSN: 1248-9204
DOI
https://doi.org/10.1007/s10029-014-1241-9

Weitere Artikel der Ausgabe 4/2015

Hernia 4/2015 Zur Ausgabe

Update Chirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

S3-Leitlinie „Diagnostik und Therapie des Karpaltunnelsyndroms“

Karpaltunnelsyndrom BDC Leitlinien Webinare
CME: 2 Punkte

Das Karpaltunnelsyndrom ist die häufigste Kompressionsneuropathie peripherer Nerven. Obwohl die Anamnese mit dem nächtlichen Einschlafen der Hand (Brachialgia parästhetica nocturna) sehr typisch ist, ist eine klinisch-neurologische Untersuchung und Elektroneurografie in manchen Fällen auch eine Neurosonografie erforderlich. Im Anfangsstadium sind konservative Maßnahmen (Handgelenksschiene, Ergotherapie) empfehlenswert. Bei nicht Ansprechen der konservativen Therapie oder Auftreten von neurologischen Ausfällen ist eine Dekompression des N. medianus am Karpaltunnel indiziert.

Prof. Dr. med. Gregor Antoniadis
Berufsverband der Deutschen Chirurgie e.V.

S2e-Leitlinie „Distale Radiusfraktur“

Radiusfraktur BDC Leitlinien Webinare
CME: 2 Punkte

Das Webinar beschäftigt sich mit Fragen und Antworten zu Diagnostik und Klassifikation sowie Möglichkeiten des Ausschlusses von Zusatzverletzungen. Die Referenten erläutern, welche Frakturen konservativ behandelt werden können und wie. Das Webinar beantwortet die Frage nach aktuellen operativen Therapiekonzepten: Welcher Zugang, welches Osteosynthesematerial? Auf was muss bei der Nachbehandlung der distalen Radiusfraktur geachtet werden?

PD Dr. med. Oliver Pieske
Dr. med. Benjamin Meyknecht
Berufsverband der Deutschen Chirurgie e.V.

S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“

Appendizitis BDC Leitlinien Webinare
CME: 2 Punkte

Inhalte des Webinars zur S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“ sind die Darstellung des Projektes und des Erstellungswegs zur S1-Leitlinie, die Erläuterung der klinischen Relevanz der Klassifikation EAES 2015, die wissenschaftliche Begründung der wichtigsten Empfehlungen und die Darstellung stadiengerechter Therapieoptionen.

Dr. med. Mihailo Andric
Berufsverband der Deutschen Chirurgie e.V.